Differences in Cardiometabolic Proteins in Pregnancy Prioritize Relevant Targets of Preeclampsia.

BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by widespread vascular inflammation. It occurs frequently in pregnancy, often without known risk factors, and has high rates of maternal and fetal morbidity and mortality. Identification of biomarkers that predict preeclampsia and its cardiovascular sequelae before clinical onset, or even before pregnancy, is a critical unmet need for the prevention of adverse pregnancy outcomes. METHODS: We explored differences in cardiovascular proteomics (Olink Explore 384) in 256 diverse pregnant persons across 2 centers (26% Hispanic, 21% Black). RESULTS: We identified significant differences in plasma abundance of markers associated with angiogenesis, blood pressure, cell adhesion, inflammation, and metabolism between individuals delivering with preeclampsia and controls, some of which have not been widely described previously and are not represented in the preeclampsia placental transcriptome. While we observed a broadly similar pattern in early (<34 weeks) versus late (≥34 weeks) preeclampsia, several proteins related to hemodynamic stress, hemostasis, and immune response appeared to be more highly dysregulated in early preeclampsia relative to late preeclampsia. CONCLUSIONS: These results demonstrate the value of performing targeted proteomics using a panel of cardiovascular biomarkers to identify biomarkers relevant to preeclampsia pathophysiology and highlight the need for larger multiomic studies to define modifiable pathways of surveillance and intervention upstream to preeclampsia diagnosis.

Cancer Treatment-Related Cardiovascular Toxicity in Gynecologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Improvements in early detection and treatment of gynecologic malignancies have led to an increasing number of survivors who are at risk of long-term cardiac complications from cancer treatment. Multimodality therapies for gynecologic malignancies, including conventional chemotherapy, targeted therapeutics, and hormonal agents, place patients at risk of cancer therapy-related cardiovascular toxicity during and following treatment. Although the cardiotoxicity associated with some female predominant cancers (eg, breast cancer) have been well recognized, there has been less recognition of the potential adverse cardiovascular effects of anticancer therapies used to treat gynecologic malignancies. In this review, the authors provide a comprehensive overview of the cancer therapeutic agents used in gynecologic malignancies, associated cardiovascular toxicities, risk factors for cardiotoxicity, cardiac imaging, and prevention strategies.

Management of the Fontan patient during pregnancy.

PURPOSE OF REVIEW: Patients with single-ventricle Fontan palliation surgery often wish to pursue pregnancy. Pregnancies should be planned with well tolerated and effective contraception, and preconception risk stratification by adult congenital heart disease and maternal foetal medicine specialists. RECENT FINDINGS: Although infertility and foetal complications, including pregnancy loss, preterm birth and foetal growth restriction, are common, most patients with Fontan palliations can successfully complete pregnancy with a team-based approach. Important risk predictors are resting oxygen saturations, baseline functional status and the presence of systemic complications of the Fontan repair, including advanced Fontan associated liver disease, plastic bronchitis and ventricular dysfunction. Common maternal cardiovascular complications include arrhythmia, heart failure and thromboembolism. Delivery planning with input from an obstetric anaesthesiologist who has knowledge of complex congenital heart defects can facilitate appropriate, individualized monitoring and pain control. A vaginal delivery with consideration of an assisted second stage is appropriate for most single ventricle patients, in the absence of obstetric or foetal indications for caesarean delivery. Close postpartum monitoring and follow up is recommended, as the early postpartum period is the highest risk time for cardiovascular complications in patients with congenital heart disease. SUMMARY: A multidisciplinary approach to managing pregnancy and delivery in patients with Fontan circulation facilitates optimal maternal and infant outcomes.

Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.

Prenatal Low-Dose Aspirin Use Associated with Reduced Incidence of Postpartum Hypertension among Women with Preeclampsia.

OBJECTIVE: Postpartum hypertension (PP-HTN), defined as systolic/diastolic blood pressure (SBP/DBP) ≥140/90, on two occasions at least 4 hours apart after delivery occurs in up to 50% of preeclamptic pregnancies, and is associated with adverse maternal outcomes. Excessive production of antiangiogenic factors (i.e., soluble fms-like tyrosine kinase 1 [sFLT1]) and reduced levels of proangiogenic factors (i.e., placental growth factor [PlGF]) are associated with preeclamptic pregnancies. The aim of this study was to identify clinical risk factors and/or serum biomarkers associated with PP-HTN in preeclampsia. STUDY DESIGN: Preeclamptic women (n = 82, aged ≥18 years) were prospectively enrolled in an observational study. Serial blood pressures were obtained through the labor course and until 48 hours postpartum, and serum was obtained within 24 hours postpartum. Statistical analysis was performed by using Student's two-tailed t-test and Fisher's exact test. RESULTS: Baseline comorbidities and antihypertensive use were similar among those who developed PP-HTN and those who did not. Among preeclamptic patients, 33% developed PP-HTN; these had significantly more severe preeclampsia features versus no PP-HTN (96 vs. 78%, p = 0.05). PP-HTN was associated with higher re-hospitalization rates (26 vs. 6%, p = 0.01). Among those taking low-dose aspirin (ASA) for preeclampsia prophylaxis (n = 12), PP-HTN was significantly less frequent versus those not taking low-dose ASA (0 vs. 22%, p = 0.007). Low-dose ASA use was associated with significantly lower peripartum sFLT1 levels (4,650 ± 2,335 vs. 7,870 ± 6,282 pg/mL, p = 0.03) and sFLT1/PlGF ratio (397 ± 196 vs. 1,527 ± 2,668, p = 0.03). CONCLUSION: One-third of women with preeclampsia develop PP-HTN; these patients have more severe preeclampsia and have higher re-hospitalization rates. Prenatal low-dose ASA use was associated with significantly lower incidence of PP-HTN, reduced levels of antiangiogenic factors, and lower 6-week re-hospitalization rates. These findings, if replicated, may have clinical implications on the use of low-dose ASA during pregnancy to reduce incidence of postpartum HTN. KEY POINTS: · Postpartum hypertension is common in preeclampsia.. · Prenatal aspirin may reduce postpartum hypertension.. · Prenatal aspirin may reduce sFLT1 levels..

Cardiac Surgery in Women in the Current Era: What Are the Gaps in Care?

Cardiovascular disease remains the leading cause of morbidity and mortality for women in United States and worldwide. One in 3 women dies from cardiovascular disease, and 45% of women >20 years old have some form of CVD. Historically, women have had higher morbidity and mortality after cardiac surgery. Sex influences pathogenesis, pathophysiology, presentation, postoperative complications, surgical outcomes, and survival. This review summarizes current cardiovascular surgery outcomes as they pertain to women. Specifically, this article seeks to address whether sex disparities in research, surgical referral, and outcomes still exist and to provide strategies to close these gaps. In addition, with the growing population of women of reproductive age with cardiovascular disease and cardiovascular risk factors, indications for cardiac surgery arise in pregnant women. The current review will also address the unique issues associated with this special population.

Summary of Updated Recommendations for Primary Prevention of Cardiovascular Disease in Women: JACC State-of-the-Art Review.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for women in the United States and worldwide. There has been no American College of Cardiology (ACC)/American Heart Association guideline update specifically for the prevention of CVD in women since 2011. Since then, the body of sex-specific data has grown, in addition to updated hypertension, cholesterol, diabetes, atrial fibrillation, and primary prevention guidelines. The ACC CVD in Women Committee undertook a review of the recent guidelines and major studies to summarize recommendations pertinent to women. In this update, the authors address special topics, particularly the risk factors and treatments that have led to some controversies and confusion. Specifically, sex-related risk factors, hypertension, diabetes, hyperlipidemia, anticoagulation for atrial fibrillation, use of aspirin, perimenopausal hormone therapy, and psychosocial issues are highlighted.

The Spectrum of Pregnancy-Associated Heart Failure Phenotypes: An Echocardiographic Study.

Compare echocardiographic phenotypes of women presenting with peripartum heart failure. A retrospective case-control study of pregnant women (n = 86) presenting with PP-HF symptoms (i.e., dyspnea, PND, orthopnea) and objective examination and laboratory findings (lung congestion, elevated JVP and/or HJR, elevated brain natriuretic peptide [BNP] and pulmonary edema on chest X-ray). Three distinct phenotypes based on echocardiographically-defined LVEF were identified: (a) PP-HF with preserved ejection fraction (PP HFpEF, LVEF: > 50%); (b) PP-HF with midrange ejection fraction (PP HFmrEF, LVEF: 40-50%); c) PP-HF with reduced ejection fraction (PP HFrEF, LVEF: < 40%); these were compared with 17 pregnant subjects without PP-HF symptoms/findings. Most patients were African American (n = 63; 73%), with low prevalence of hypertension (n = 15, 17%) or diabetes mellitus (n = 5, 5%); pre-eclampsia was highly prevalent (n = 52, 60%). Echocardiographically-defined phenotypes (HFpEF, n = 37; HFmrEF, n = 18; HFrEF, n = 31) showed progressively worse abnormalities in LV remodeling (LV enlargement, LV hypertrophy), LV diastolic function, and right ventricular function; the three PP-HF groups had comparable abnormalities in increased left atrial size and estimated peak tricuspid valve regurgitation velocity. Compared to controls, all three groups had significantly increased filling pressures, LV mass index and left atrial volume index. Peripartum women presenting with the clinical syndrome of heart failure exhibit a spectrum of echocardiographic phenotypes. Significant abnormalities in LV structure, diastolic function, LA size, peak TR velocity and RV function were identified in women with preserved and mid-range EFs, suggesting pregnancy-related cardiac pathophysiologic derangements.

Pregnancy after Aortic Root Replacement in Marfan's Syndrome: A Case Series and Review of the Literature.

Objectives We sought to characterize pregnancy-related aortic complications in women with Marfan's syndrome who had prior aortic root replacement. Study Design This is a retrospective case series study and literature review of women with Marfan's syndrome with pregnancy after aortic root replacement. We surveyed women with Marfan's syndrome who had successful pregnancy after aortic root replacement using the Marfan Foundation Website and from two large tertiary care Marfan's clinics. Clinical data, counseling information, and details of pregnancy-related aortic complications were compiled. A literature review was performed assessing aortic outcomes in women with Marfan's syndrome with pregnancy after aortic surgery. Results Fourteen women with 20 pregnancies were identified. Two women had three pregnancies following root replacement for aortic dissection. There were no aortic dissections during the 20 pregnancies. In contrast, aortic dissection was frequently reported in the literature. Conclusions Women with Marfan's syndrome who become pregnant following aortic root replacement remain at risk for distal aortic dissection related to pregnancy. The exact risk is difficult to quantify but is not zero and women should be counseled accordingly.

Impact of pregnancy on autograft dilatation and aortic valve function following the Ross procedure.

OBJECTIVE: The effects of pregnancy on autograft dilatation and neoaortic valve function in patients with a Ross procedure have not been studied. We sought to evaluate the effect of pregnancy on autograft dilatation and valve function in these patients with the goal of determining whether pregnancy is safe after the Ross procedure. DESIGN: A retrospective chart review of female patients who underwent a Ross procedure was conducted. PATIENTS: Medical records for 51 patients were reviewed. Among the 33 patients who met inclusion criteria, 11 became pregnant after surgery and 22 did not. OUTCOME MEASURES: Echocardiographic reports were used to record aortic root diameter and aortic insufficiency before, during, and after pregnancy. Patient's charts were reviewed for reinterventions and complications. Primary endpoints included reinterventions, aortic root dilation of ≥5 cm, aortic insufficiency degree ≥ moderate, and death. RESULTS: There were 18 pregnancies carried beyond 20 weeks in 11 patients. There was no significant difference in aortic root diameter between nulliparous patients and parous patients prior to their first pregnancy (3.53 ± 0.44 vs 3.57 ± 0.69 cm, P = .74). There was no significant change in aortic root diameter after first pregnancy (3.7 ± 0.4 cm, P = .056) although there was significant dilatation after the second (4.3 ± 0.7 cm, P = .009) and third (4.5 ± 0.7 cm, P = .009) pregnancies. Freedom from combined endpoints was significantly higher for patients in the pregnancy group than those in the nonpregnancy group (P = .002). CONCLUSIONS: Pregnancy was not associated with significantly increased adverse events in patients following the Ross procedure. Special care should be taken after the first pregnancy, as multiparity may lead to increased neoaortic dilatation.

Repeat revascularisation outcomes after percutaneous coronary intervention in patients with rheumatoid arthritis.

OBJECTIVE: To investigate repeat revascularisation outcomes in patients with rheumatoid arthritis(RA) after percutaneous coronary intervention (PCI). METHODS: We performed a single-centre, retrospective matched cohort study of patients with RA matched to non-RA patients post PCI. Primary endpoints were time to target lesion revascularisation (TLR) and target vessel revascularisation (TVR) analysed by Cox proportional hazard shared frailty models. RESULTS: A total of 228 lesions (143 patients) were identified in the RA cohort and matched to 677 control lesions (541 patients). TLR occurred in 33% (n=75) of RA lesions versus 25% (n=166) of control lesions (adjusted HR 1.3; 95% CI 0.97 to 1.8). TVR occurred in 39% (n=89) of RA lesions versus 31% (n=213) of control lesions (adjusted HR 1.15; 95% CI 0.82 to 1.6). There was a significant hazard for TLR (adjusted HR 1.48; 95% CI 1.03 to 2.13) and TVR (adjusted HR 1.55; 95% CI 1.12 to 2.14) when excluding lesions with revascularisation events or follow-up less than 1 year. When stratified by treatment with methotrexate or tumour necrosis factor (TNF) α inhibitors or both at discharge, lesions from patients with RA treated with these agents had similar TVR and TLR as control lesions, whereas lesions from patients with RA not treated with these agents had significantly more TLR and TVR (TLR adjusted HR 1.48; 95% CI 1.08 to 2.03; TVR adjusted HR 1.38; 95% CI 1.04 to 1.84). CONCLUSIONS: RA predisposes to repeat revascularisation, specifically in patients followed after the 1-year landmark. In the absence of RA treatments including methotrexate and/or TNFα inhibitors, RA is associated with a 50% increased relative risk of repeat revascularisation following PCI. These findings emphasise the adverse effects of chronic inflammation on the durability of PCI and provide further support for aggressive anti-inflammatory treatment in patients with RA.

Antibody-mediated rejection of the heart in the setting of autoimmune demyelinating polyneuropathy: a case report and review of the literature.

Background. Antibody-mediated rejection (AMR) is caused by the production of donor-specific antibodies (DSA) which lead to allograft injury in part via complement activation. The inflammatory demyelinating polyneuropathies (IDP) are inflammatory disorders of the nervous system, involving both cellular and humoral immune mechanisms directed against myelin. Case Report. A 58-year-old man five years after heart transplant presented with progressive dyspnea, imbalance, dysphagia, and weakness. Nerve conduction studies and electromyogram were consistent with IDP. Plasmapheresis and high-dose steroids resulted in improvement in neurologic symptoms. Within two weeks, he was readmitted with anasarca and acute renal failure, requiring intravenous furosemide and inotropic support. Echocardiogram and right heart catheterization revealed reduced cardiac function and elevated filling pressures. DSA was positive against HLA DR53, and endomyocardial biopsy revealed grade 1R chronic inflammation, with strong capillary endothelial immunostaining for C4d. Plasmapheresis and intravenous immunoglobulin (IVIG) were initiated. His anasarca and renal failure subsequently resolved, echocardiogram showed improved function off inotropes, and anti-DR53 MFI was reduced by 57%. Conclusions. This is an example of a single immune-mediated process causing concurrent IDP and AMR. The improvement in cardiac function and neurologic symptoms with plasmapheresis, IVIG, and high-dose steroids argues for a unifying antibody-mediated mechanism.